Stroke is one of the most common causes of disability and there is tremendous room for improvement in rehabilitation techniques. While neural plasticity likely supports much natural and practice-related recovery, such naturally occurring mechanisms for plasticity could be potentially enhanced to improved functional outcomes. We propose a hybrid approach to combining transcranial magnetic stimulation, long seen as an adjunctive method in neurorehabilitation, with upper extremity robotic therapy, another promising method. Our preliminary data shows the potential of brain stimulation to measure and induce plasticity in the motor cortex. We plan to: 1. Determine parameters of stimulation timing that enhance plasticity in normal volunteers;2. Determine parameters of stimulation location that enhance plasticity in normal volunteers;and 3. Determine feasibility and pilot data regarding effectiveness in chronic stroke patients. The resulting methods will be applicable to a wide range of motor disability found in stroke survivors and a wide range of methods that combine motor practice with other stimuli, whether natural (such as visual cuing) or artificial (such as magnetic stimulation.) When we have accomplished these aims, we will have established methods that can be used in a larger, multi-site clinical trial of combined stimulation and upper extremity robotic rehabilitation, and will also have uncovered valuable basic mechanisms regarding the induction of motor cortical plasticity through a precisely timed combination of stimulation and repetitive practice of movement in both normal and stroke affected populations. The data obtained by completing these aims will greatly impact future design of stroke rehabilitation paradigms. PUBLIC HEALTH RELEVANCE: Many individuals with stroke remain severely limited in their participation in life tasks because of decreased functional use of the affected arm. Change in connections between nerve cells in the brain appears to help people get better, but it may be possible to increase the amount of useful change by stimulating the brain with magnetic fields. We plan to combine brain stimulation with specialized rehabilitation robots, work out the right way to combine stimulation with practice of reaching movements, and test the combination in people with stroke.